A series of controlled studies is proposed to elucidate psychopharmacologic, pharmacokinetic and epidemiologic aspects of cocaine in man. Specifically, the research is designed to: 1. Study epidemiological aspects of cocaine use in an opiate-dependent population by ascertaining through questionnaire the incidence, degree and history of its use, and evaluate a subgroup for patterns of cocaine use over time that will be correlated with naltrexone, methadone and placebo treatments; 2. Devise a standard procedure for measuring subjective, behavioral and physiologic effects of cocaine and use these procedures to establish dose-response curves and the time-course of its effects when acutely administered intranasally and intravenously; 3. Determine the efficacy of detecting cocaine use by two methods of analyzing urine for cocaine metabolites; 4. Determine the rate of absorption and elimination of acutely administered intranasal and intravenous cocaine, and correlate plasma levels and other pharmacokinetic data with the onset and duration of subjective, behavioral and physiologic effects; 5. Evaluate the degree to which potential cocaine antagonists block acute effects of cocaine and the efficacy of treatment with a cocaine antagonist in reducing the incidence of illicit cocaine use.